Universal Scaffold for an Activatable Photosensitizer with Completely Inhibited Photosensitivity

Zhai, WH (Zhai, Wenhao)^{[ 1 ]} ; Zhang, YK (Zhang, Yongkang)^{[ 1 ]} ; Liu, M (Liu, Ming)^{[ 1 ]} ; Zhang, H (Zhang, Hao)^{[ 1 ]} ; Zhang, JQ (Zhang, Junqing)^{[ 1 ]} ; Li, CH (Li, Changhua)^{[ 1 ]}

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 2019

DOI: 10.1002/anie.201907510

摘要

Activatable photosensitizers (aPSs) sensitive to specific stimuli hold potential for targeting multiple disease biomarkers and are desirable for photodynamic therapy (PDT). Presented herein is the design of aPSs that can be activated and fully recover from an inhibited state in the presence of specific biomarker. A designed long-wavelength D-pi-A photosensitizer, PSSe-I, with highly efficient photosensitivity for generation of O-1(2) was used. Caging of the phenolate donor of PSSe-I with a biomarker-sensitive group provided (PS)-P-ALP, and the drastic activation of its photosensitivity was demonstrated intracellularly. To enhance the flexibility of the design strategy, a clickable azide group was introduced into the scaffold to allow integration of more functionality. Modularly derived mito-PNPS, equipped with a mitochondria-targeting group and a specific peroxynitrite-reactive trigger, was synthesized and demonstrated superior performance in cells. This strategy could lead to customization of aPSs applicable to a specific PDT.